Circular RNA circ_0000119 promotes cervical cancer cell growth and migration via miR-433-3p/PAK2 axis.

The purpose of this study was to investigate the role of circ_0000119 on CC progression and its molecular mechanism. The expression levels of circ_0000119, miR-433-3p, and p21-activated kinase 2 (PAK2) in CC tissues and cell lines were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was assessed using 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, 5-Ethynyl-2'-deoxyuridine (EdU) assay and colony formation assay. Cell cycle and apoptosis were assessed by flow cytometry. Cell migration and invasive ability were examined by Transwell assays. Downstream binding targets of circ_0000119 were predicted by online bioinformatics tools and confirmed by dual luciferase reporter gene assay, RNA immunoprecipitation (RIP) assay, and RNA pull-down assay. The role of circ_0000119/miR-433-3p/PAK2 axis in regulating the CC process was explored by rescue experiments. A xenograft model was constructed to further determine the effect of circ_0000119 on CC tumor growth in vivo. Immunohistochemistry (IHC) assay was conducted for Ki67 expression. Circ_0000119 was aberrantly upregulated in CC tissues and cell lines. Knockdown of circ_0000119 inhibited CC cell proliferation, cell cycle progress, migration, invasion, and promoted apoptosis of CC cells. MiR-433-3p was a binding target of circ_0000119, and PAK2 was a downstream gene of miR-433-3p. MiR-433-3p inhibition reversed the inhibitory effect of silencing circ_0000119 on CC progression. In addition, PAK2 overexpression reversed the effect of miR-433-3p on CC progression. PAK2 expression was regulated by circ_0000119 and miR-433-3p. Moreover, circ_0000119 knockdown reduced tumor growth of CC in vivo. Circ_0000119 was upregulated in CC, and circ_0000119 knockdown suppressed CC malignant development through the miR-433-3p/PAK2 axis.

A comparison of Doppler measures of ovarian blood flow between women with and without ovarian dysfunction and correlations of Doppler indices with ovarian dysfunction markers: a meta-analysis.

Background: Doppler ultrasonography is used to study ovarian vascular characteristics. However, the outcomes are reported with a considerable variability in literature. Here we review the differences in Doppler ultrasound-measured ovarian blood flow indices between women with and without ovarian dysfunction and seeks correlations between Doppler measures and ovarian markers. Methods: A literature search was conducted in electronic databases (Google Scholar, Ovid, PubMed, Science Direct, and Springer) to identify studies that used Doppler for ovarian blood flow examination and reported Doppler measures in women with and without ovarian dysfunction and/or the correlations between wDoppler indices and markers of ovarian dysfunction. After quality assessment of included studies, a meta-analysis of weighted mean differences (WMDs) between women with and without ovarian dysfunction in vascularization index (VI), flow index (FI), vascularization flow index (VFI), pulsatility index (PI) and resistance index (RI) was performed. Correlation coefficients between Doppler indices and markers of ovarian dysfunction were pooled to achieve overall estimates. Results: A total of 27 studies [2,377 women with ovarian dysfunction and 308 controls; age 27.7 years, 95% confidence interval (CI): 26.4 to 29.1] were included. These studies were of moderate quality. The VI (WMD 9.75; P<0.0001), FI (WMD 2.73; P<0.0001), and VFI (WMD 1.29; P<0.0001) were significantly higher whereas PI (WMD -1.08; P=0.001) and RI (WMD -0.26; P<0.0001) were significantly lower in women with polycystic ovarian syndrome (PCOS) than in normal women. In women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI), antral follicle count was positively correlated with VI (r=0.24; P=0.001), FI (r=0.42; P<0.0001), and VFI (r=0.25; P=0.002). In women with PCOS, testosterone had statistically non-significant correlations with VI (r=0.40; P=0.081), and VFI (r=0.39; P=0.063) and was inversely correlated with PI (r=-0.30; P<0.0001) and RI (r=-0.48; P<0.0001). In women with PCOS, luteinizing hormone (LH) was inversely correlated with PI (r=-0.26; P=0.086) and RI (r=-0.25; P=0.007). Conclusions: Doppler indices are found significantly different in women with and without ovarian dysfunction and have significant correlations with markers of ovarian dysfunction. These results support the use of Doppler ultrasound to examine ovarian dysfunction. High statistical heterogeneity observed herein should be studies in future investigations.

LncRNA CERS6-AS1, sponging miR-6838-5p, promotes proliferation and invasion in cervical carcinoma cells by upregulating FOXP2.

Cervical cancer (CC) is a common disease in women characterized by high recurrence rate. LncRNA ceramide synthase 6 antisense RNA 1 (CERS6-AS1) has been found to play a crucial role in the progression of breast cancer and pancreatic cancer. Nevertheless, the regulatory role of CERS6-AS1 in CC remains largely unclear. Here, we found that the expression of CERS6-AS1 was upregulated in CC tissues and cell lines compared with adjacent tissues and normal human cervical epithelial cells. CERS6-AS1 overexpression promoted proliferation and invasion, and inhibited apoptosis in CC cells, while silencing of CERS6-AS1 led to the opposite results. CERS6-AS1 was verified as a sponge of miR-6838-5p by RNA pull-down and luciferase reporter gene assays. Functional investigations revealed that CERS6-AS1 knockdown inhibited proliferation and invasion, and promoted apoptosis in CC cells, which was reversed by miR-6838-5p inhibitor. Furthermore, forkhead box P2 (FOXP2) was identified as a target for miR-6838-5p, and overexpression of miR-6838-5p decreased the expression level of FOXP2. Besides, CERS6-AS1 was able to sponge miR-6838-5p to accelerate CC cell proliferation and invasion and inhibited cell apoptosis through upregulating FOXP2 expression. In general, CERS6-AS1 was able to regulate CC cell proliferation, invasion and apoptosis by the miR-6838-5p/FOXP2 axis, which suggested that CERS6-AS1 may be a potential target for the treatment of CC.

Anticancer activity of 23,24-dihydrocucurbitacin B against the HeLa human cervical cell line is due to apoptosis and G2/M cell cycle arrest.

[This retracts the article DOI: 10.3892/etm.2018.5710.].

Cisplatin plus paclitaxel chemotherapy with or without bevacizumab in postmenopausal women with previously untreated advanced cervical cancer: a retrospective study.

BACKGROUND: The aim of this study was to assess the survival outcomes of cisplatin-paclitaxel chemotherapy plus bevacizumab (CPB) versus cisplatin-paclitaxel chemotherapy alone (CPA) in postmenopausal women with previously untreated advanced cervical cancer (CC). METHODS: Consecutive postmenopausal women who experienced CPB or CPA were identified retrospectively from our medical centre during 2015-2019. Follow-up visits occurred 1 and 3 months after starting CPB or CPA. Afterwards, this assessment was conducted every 3 months for 1 year and then yearly thereafter. The primary endpoints were overall survival (OS) and progression-free survival (PFS); secondary endpoints were the frequency and severity of adverse events (AEs). RESULTS: Two hundred forty-six postmenopausal women were included (CPB, n = 124; CPA, n = 122). The median follow-up for the entire cohort was 24 months (range, 2-32). At the final follow-up, a significant difference was detected in terms of median OS (16.4 months [95% CI, 15.3-17.1] for CPB vs. 12.3 months [95% CI, 10.2-13.5] for CPA; hazard ratio (HR) 0.69, 95% CI, 0.49-0.99; p = 0.001), and the median PFS was longer in the CPB group than in the CPA group (9.2 months [95% CI, 8.3-10.7] vs. 7.9 months (95% CI, 6.1-8.6) (HR 0.62, 95% CI, 0.47-0.82; p < 0.001). There were significant differences in the number of AEs between the groups (hypertension grade ≥ 2 [p < 0.001], neutropenia grade ≥ 4 [p < 0.001], and thrombosis/embolism grade ≥ 3 [p = 0.030]). CONCLUSIONS: Among postmenopausal women with previously untreated advanced CC, those who received CPB experienced superior survival benefits compared to those who received CPA. The safety profile for CPB was controllable despite the long duration of CPB use.

Retracted Article: Knockdown of TMPRSS11D inhibits the proliferation, migration and invasion of cervical cancer cells.

TMPRSS11D is a member of the type II transmembrane serine proteases (TTSPs) family that is implicated in the development and progression of several cancers. However, the biological roles of TMPRSS11D in cervical cancer have not been investigated. In the present study, we detected the expression levels of TMPRSS11D in human cervical cancer tissues and cell lines. The results showed that TMPRSS11D expression was significantly upregulated in cervical cancer tissues as compared to the adjacent normal tissues. Besides, TMPRSS11D was highly expressed in human cervical cancer cell lines. Then we knocked down TMPRSS11D in cervical cancer cell lines to evaluate the effects of TMPRSS11D knockdown on cervical cancer cells. The results showed that knockdown of TMPRSS11D significantly suppressed cell proliferation, migration and invasion in cervical cancer cell lines. Furthermore, the data revealed that TMPRSS11D knockdown prevented epithelial-mesenchymal transition (EMT), as proved by the increased E-cadherin expression, as well as decreased N-cadherin and fibronectin expressions. Additionally, knockdown of TMPRSS11D inhibited the activation of the PI3K/Akt pathway in cervical cancer cells. Furthermore, insulin-like growth factor-1 (IGF-1) treatment reversed the inhibitory effects of TMPRSS11D knockdown on cell proliferation and migration. Collectively, knockdown of TMPRSS11D exerted anti-tumor activity, at least in part, via inhibiting the PI3K/Akt pathway. These findings indicated that TMPRSS11D might serve as a novel therapeutic target for the treatment of cervical cancer.

Anticancer activity of 23,24-dihydrocucurbitacin B against the HeLa human cervical cell line is due to apoptosis and G2/M cell cycle arrest.

Cervical cancer is one of the primary causes of cancer-associated mortality worldwide. Due to the increasing incidence of cervical cancer, multiple treatment options are required. Initial responses to chemotherapy and surgical interventions are generally positive, however patients often experience relapse and tumor recurrence. Currently, the effects of cucurbitacins on different types of cancer are being investigated, as they exhibit a wide variety of bioactivities. The anticancer activity of the cucurbitacin 23,24-dihydrocucurbitacin B against a panel of human cervical cancer cell lines was investigated in the current study. Cell viability was determined using an MTT assay and apoptosis was detected using DAPI staining. The proportion of apoptotic cells, cell cycle distribution, mitochondrial membrane potential (ΔΨm) and reactive oxygen species (ROS) levels were estimated using flow cytometry. Protein expression was determined using western blot analysis. The results of the current study indicated that 23,24-dihydrocucurbitacin B inhibited the viability of human cervical cancer cell lines and had an IC50 of 40-60 µM. However, its cytotoxic effects were much less pronounced in normal epithelial fr2 and HerEpiC cells, where it had an IC50 of 125 µM. The underlying mechanisms of this were further studied and the results demonstrated that 23,24-dihydrocucurbitacin B induced apoptosis in HeLa cells and caused ROS-mediated shifts in the ΔΨm. Additionally, it caused the cell cycle arrest of HeLa cells at the G2/M checkpoint. The phosphoinositide 3 kinase/protein kinase B/mechanistic target of rampamycin (PI3K/AKT/mTOR) cascade may serve an important role in cancer tumorigenesis, progression and resistance to chemotherapy. The results indicated that 23,24-dihydrocucurbitacin B significantly decreased the expression of important proteins in the PI3K/Akt/mTOR cascade. Taken together, these results suggest that 23,24-dihydrocucurbitacin B may be novel method of treating cervical cancer.

Prospects of Contrast-Enhanced Ultrasonography for the Diagnosis of Peripheral Arterial Disease: A Meta-analysis.

OBJECTIVES: Contrast-enhanced ultrasonography (CEUS) is a modern diagnostic method that can also be used to study microperfusion. This study compared the time to peak intensity measured by CEUS in patients with peripheral arterial disease (PAD) and healthy control participants. METHODS: After a comprehensive literature search in multiple electronic databases and study selection, a random-effect meta-analysis was performed to compare the time to peak intensity measured by CEUS in patients with PAD and healthy controls, which followed meta-regression analyses for identification of factors affecting the outcomes. RESULTS: Fourteen studies (data for 322 patients with PAD and 314 healthy individuals) were used for the meta-analysis. The age of this sample of patients with PAD was 64.92 (95% confidence interval, 62.53, 67.31) years, and that of the healthy controls was 55.32 (51.67, 58.98) years. The times to peak intensity were 18.55 (15.62, 21.48) seconds in healthy controls, 33.40 (27.65, 39.15) seconds in patients with PAD, and 76.22 (36.23, 116.22) seconds in patients with PAD and diabetes mellitus. The difference between patients with PAD and healthy controls in the time to peak intensity was statistically significant (mean difference, 24.80 [10.16, 39.44] seconds; P < .00009). The ABI was not significantly associated with the time to peak intensity in patients with PAD. Age and sex were also not significantly associated with the time to peak intensity. CONCLUSIONS: Contrast-enhanced ultrasonography is a valuable tool for the diagnosis of PAD based on its ability to differentiate the time to peak intensity between patients with PAD and healthy individuals, but little data are yet available to assess its diagnostic ability in clinical practice.

Tripartite Motif 16 Inhibits the Migration and Invasion in Ovarian Cancer Cells.

Tripartite motif 16 (TRIM16), a member of the RING B-box coiled-coil (RBCC)/tripartite motif (TRIM) protein family, has been shown to play a role in tumor development and progression. However, the role of TRIM16 in ovarian cancer has never been revealed. Thus, in this study, we investigated the roles and mechanisms of TRIM16 in ovarian cancer. Our results demonstrated that TRIM16 expression was low in ovarian cancer cell lines. In addition, overexpression of TRIM16 significantly inhibited the migration and invasion in vitro, as well as suppressed the epithelial-mesenchymal transition (EMT) phenotype in ovarian cancer cells. Furthermore, overexpression of TRIM16 greatly inhibited the protein expression levels of Shh, Smo, Ptc, Gli-1, MMP2, and MMP9 in ovarian cancer cells. Taken together, these results strongly suggest that TRIM16 inhibits the migration and invasion via suppressing the Sonic hedgehog signaling pathway in ovarian cancer cells. Thus, TRIM16 may be a novel potential therapeutic target for ovarian cancer.

[Impact of intrauterine device insertion surgery on women's mental state].

OBJECTIVE: To evaluate the impact of the intrauterine device (IUD) insertion on the mental state of women. METHODS: From Jan. 2009 to Jun. 2010, a multi-center clinical observational study was performed. Totally 641 women were selected in the six provinces' 18 family planning service stations and hospitals for IUD insertion surgery study. Analysis of the change of women's mental state which was evaluated by symptom checklist-90 (SCL-90) scale before and after IUD insertion surgery. RESULTS: Before and after IUD insertion surgery, 10 factors' scores in SCL-90 of the observed objects were between 1.1 to 1.2, total scores were 107±27 and 105±25, respectively. Before and after surgery, total average score both were 1.2, the average score of positive items both were 2.1. The difference of the above results were not statistically significance (all P>0.05). Preoperative and postoperative, the rate of positive items was 9.2%-19.6% and 7.7%-17.6%, respectively.In addition to anxiety and fear, the rate of other factors' positive items postoperative was significantly lower than those in the preoperative (all P<0.05). The incidence of the observed objects postoperative of each factor score, "deteriorated" was in the range of 4.9% to 23.0%, "improved" was in the range of 26.3%-50.1%. The incidence of total scores, "deterioration" was 28.8% (166/575), "improved" was 45.6% (262/575). The incidence of the average score of positive items, "deterioration" was 3.7% (21/575), "improved" was 52.3% (301/575). Logistic analysis showed that, in addition to unit level, there were no other significant influencing factors for women' mental state of postoperative (all P>0.05). CONCLUSION: IUD insertion surgery has no adverse effect on women's mental state.